紫花前胡素通过激活PPAR信号通路抑制髓核细胞凋亡  

Decursin inhibits apoptosis of nucleus pulposus cells by activating the PPAR signaling pathway

作　　者：王冰钰 邓志军 胡涛 李颢颜 郭洁文 WANG Bingyu;DENG Zhijun;HU Tao;LI Haoyan;GUO Jiewen(Department of Pharmacy,The Affiliated TCM Hospital of Guangzhou Medical University,Guangzhou 510130,Guangdong,China)

机构地区：[1]广州医科大学附属中医医院药学部,广东广州510130

出　　处：《广州医科大学学报》2024年第3期11-18,共8页Academic Journal of Guangzhou Medical University

摘　　要：目的:探讨紫花前胡素(DE)抑制髓核细胞凋亡的作用及其机制。方法:体外培养大鼠原代髓核细胞,使用肿瘤坏死因子α(TNF-α)构建椎间盘退变(IDD)模型。采用CCK-8法检测不同浓度DE对IDD模型髓核细胞活力的影响,并确定DE的最佳实验浓度进行后续实验。采用TUNEL染色、流式细胞术和免疫印迹法检测DE对髓核细胞凋亡的影响。采用转录组测序技术(RNA-seq)检测并使用Limma包分析模型组与DE处理组基因表达差异,通过GSEA分析信号通路的变化并进行验证。结果:DE可提高IDD模型髓核细胞的活力,抑制髓核细胞凋亡(均P<0.05)。RNA-seq结果提示DE可激活过氧化物酶体增殖物激活受体(PPAR)信号通路,进一步研究证实DE通过上调PPARα表达而增加髓核细胞活力、减少髓核细胞凋亡(均P<0.05)。结论:DE通过激活PPAR信号通路抑制IDD模型髓核细胞凋亡。Objective:To investigate the effect and mechanism of decursin(DE)on inhibiting apoptosis of nucleus pulposus cells.Methods:Primary rat nucleus pulposus cells were cultured in vitro,and tumor necrosis factor-α(TNF-α)was used to construct an intervertebral disc degeneration(IDD)model.CCK-8 assay was used to detect the effect of different concentrations of DE on the viability of nucleus pulposus cells in IDD model,and the optimal experimental concentration of DE was determined for subsequent experiments.The effects of DE on apoptosis of nucleus pulposus cells were detected by TUNEL staining,flow cytometry and Western blotting.The difference of gene expression between the model group and the DE treatment group was detected by transcriptome sequencing(RNA-seq),and analyze by Limma package.Additionally,the changes in signaling pathways between the two groups were examined through GSEA analysis and further validated experimentally.Results:DE could increase the viability of nucleus pulposus cells and inhibit the apoptosis of nucleus pulposus cells in IDD model(all P<0.05).RNA-seq results suggested that DE could activate the peroxisome proliferator-activated receptor(PPAR)signaling pathway.Further studies confirmed that DE increased the viability of nucleus pulposus cells and reduced the apoptosis of nucleus pulposus cells by up-regulating PPARαexpression(all P<0.05).Conclusion:DE inhibits apoptosis of nucleus pulposus cells in IDD model by activating PPAR signaling pathway.

关 键 词：紫花前胡素 过氧化物酶体增殖物激活受体 髓核细胞 细胞凋亡 椎间盘退行性变 

分 类 号：R681.5[医药卫生—骨科学]